Nephrol Dial Transplant (2002) 17: 1487-1490
© 2002 European Renal Association-European Dialysis and Transplant Association
C2 (2-h) levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal-transplant patients
1 Department of Renal Medicine C, Skjeby Sygehus, Århus University Hospital, 2 Department of Biostatistics, University of Aarhus and 3 Department of Clinical Biochemistry, Århus Kommunehospital, Århus, Denmark
Background. Recently, 2-h samples (C2) have been found superior to trough levels for therapeutic monitoring of transplanted patients receiving cyclosporin. The present study was undertaken to see if the same was the case for tacrolimus.
Methods. Blood tacrolimus levels were determined in 21 consecutive patients at 3 and 14 days after renal transplantation, and before and 1, 2, 3, 4, and 6 h after oral intake of 0.1 mg/kg tacrolimus. The area under the blood concentration/time curve (AUC) was determined by the trapezoidal method, association between blood concentration at each sampling time and AUC by Pearson's correlation coefficient, and pairs of correlation coefficients were compared by an asymptotic Wald-type test.
Results. AUC varied five-fold despite near-equal dosing. Pearson's correlation coefficient for trough level, 1, 2, 3, 4, and 6 h were 0.84, 0.60, 0.81, 0.95, 0.95, and 0.94 on day 3 and 0.94, 0.69, 0.92, 0.96, 0.94, 0.92 on day 14. Three-, 4- and 6-h levels had significantly higher correlation coefficients compared to trough, 1- and 2-h levels. One-hour samples had significantly lower correlation coefficients compared to all other sampling times on day 14. The patient with the highest AUC developed nephrotoxicity despite trough levels in the desired range.
Conclusions. Two-hour levels are not superior to trough levels in tacrolimus-treated renal transplant patients. Despite good correlation between trough level and AUC, some patients may still receive nephrotoxic doses despite trough levels in the desired range. Sampling 3–6 h after oral intake may be at least as good as trough levels.
Keywords: area under the curve; C2 (2-h) levels; nephrotoxicity; renal-transplant patients; tacrolimus; trough levels
Correspondence and offprint requests to: Kaj Jørgensen, Research laboratory, Renal Medicine C, Skjeby Sygehus, Århus University Hospital, DK-8200 Århus N, Denmark. Email: kaj{at}dadlnet.dk
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